Faculty Spotlight: Russell Mumper, PhD
The word “nanotechnology” may sound futuristic, but as Russell Mumper, PhD, points out, the future has been around for decades.
“I’m not going to fool anybody by saying that nanotechnology is new,” says Mumper, an internationally recognized leader in applying nanotechnology to applications in pharmaceutical sciences. “ ‘Nanotechnology’ is defined by the National Nanotechnology Initiative as any type of system that has at least one dimension less than a hundred nanometers. That’s a fairly encompassing definition. There are lots of technologies that fit under that.
“For instance, liposomes have been around for more than 40 years, and they are in probably a dozen commercial products, and some of these products were approved a decade ago and meet that definition.”
However, the last ten years have seen a growing recognition of nanotechnology’s potential and an increasing ability to turn that promise into reality. Those factors, Mumper says, have sparked a nanotechnology explosion.
“People are seeing it as the next great revolution after the computer age,” he says.
Mumper is trying to make UNC-Chapel Hill a key player in that revolution. He joined the UNC Eshelman School of Pharmacy in summer 2007 as the John A. McNeill Distinguished Professor and the director of the new Center for Nanotechnology in Drug Delivery. The CNDD, part of a campus-wide nanomedicine initiative at UNC, will bring together scientists to create nano-scale pharmaceutical innovations for therapeutic and diagnostic purposes.
In addition to the CNDD, Mumper, who became the School's vice dean in 2010, has been active in other nanomedicine-related ventures on campus. He is serving as co-director of the new Institute for Nanomedicine at UNC. He has developed and is directing a campus-wide nanomedicine course. On the research front, he continues to work on two NIH-funded projects using nanotechnology to treat resistant cancer and to pursue an HIV vaccine. He also is co-investigator on a large international collaboration developing microbicides to prevent HIV infection. UNC's role in the project is to develop gel and intravaginal ring dosage forms containing a nanotechnology-based microbicde that can prevent the HIV virus from entering cells. Mumper also has been overseeing the planning for the Fourth Annual Chapel Hill Drug Conference. The conference, to be hosted by the School in May 2009, will focus on the use of nanotechnology to create safe and
effective therapeutic and diagnostic products.
Tiny Particles, Huge Potential
At sizes less than one ten-thousandth of a millimeter, nanoparticles might hold the key to overcoming some of the biggest hurdles in drug delivery, such as solubility, stability, and the need to get an otherwise potent drug inside the cell. However, for nanotechnology to be successfully applied to pharmaceutics, the products must be safe and efficacious, cost effective, and able to be mass manufactured. In the case of the nano-scale liposomal commercial products introduced a decade ago, Mumper says the difficulty and cost involved in making those liposomal drugs have prevented widespread therapeutic and commercial use.
More recently, however, more viable nano-based products have been developed commercially, helping heighten the public’s awareness of the potential of nanotechnology.
“So now people are saying, ‘OK, now we see the promise is becoming a reality in commercial products,’ Mumper says. “These new products derived from nanotechnology are helping people, proven to be safe, and have market sales in the hundreds of millions of dollars. The promise of nanotechnology was always there. However, the reduction to practice was lagging. But now it’s been reduced to practice in many areas of the pharmaceutical sciences, and these products are having visible commercial success. As a result, more money is flowing into research and development, and people are more excited about it.”
“It’s the tip of the iceberg. Part of the plan for the center is to look at the various aspects of nanotechnology and how they merge together to make this a realization.”
A Win-Win-Win-Win-Win-Win Scenario
In addition to maintaining its own staff, the CNDD will also form strong affiliations with researchers across campus. Since arriving at UNC, Mumper has been meeting with researchers from various departments who are involved in nanotechnology research to see how the center can coordinate its efforts with other related initiatives at the University.
Mumper is also drawing up a business model for the center. In his proposal, he identifies six groups of stakeholders for the CNDD: federal agencies (the National Institutes of Health and the National Science Foundation), the state of North Carolina, the University, the academic and research units on campus, UNC students, and the private sector (venture capitalists and industry).
“When I wrote the initial business model of this center, it involved a merger of the science, business, and academic objectives,” he says. “I see it as a win-win-win-win-win-win for all the stakeholders if you can achieve these three objectives.”
The center’s scientific objective will be developing nanotechnology applications to deliver drugs and vaccines more effectively. The focus will be “first in humans”—translating research into potential human clinical trials at UNC to see if a product is safe and effective. It’s an approach that correlates with the NIH’s push for more translational research.
Mumper says there has been discussion about initially focusing the center’s efforts on cancer, as well as on applying nanotechnology to diseases of the central nervous system.
“Specifically we want to be able to use nanotechnology to get either imaging agents or drugs that are normally not available to the brain—because they are not permeable at the blood-brain barrier—to enhance their delivery to the brain. That would make it easier to diagnose and treat many different types of CNS diseases, such as Alzheimer’s, Parkinson’s, and stroke.”
On the academic front, the center will strive to be the world leader in nanotechnology-related research, training, and intellectual property creation.
“This is a hot area that’s going to be at the forefront of job creation in the future,” Mumper says. “We want both professional and graduate students to be immersed in this environment, to gain skills that they otherwise won’t be able to get at universities that don’t have the commitment to this intensive investigation.”
The business goal is to create a sustainable center, which Mumper will try to accomplish by bringing in funding from an array of sources.
“The business model would ideally encompass state-sponsored support, government-sponsored support through grants and center grants, as well as a partnership with the business field, namely venture capitalists and other types of private money that would go to see the success of this enterprise,” he says.
An Industry Perspective
Mumper’s plan for funding the CNDD is similar to the way he has built his own research funding portfolio, which has totaled more than $8 million (including $6 million as principal investigator) in grants and contracts since 1999. Mumper credits his success in part to his industry experience, which began as a drug development scientist at Burroughs Wellcome in Greenville, North Carolina, after his postdoctoral fellowship at the University of Washington.
Eight years, three companies and three cross-country moves later, Mumper decided to look for something with more stability for his family when the company he was working for at the time, ViroTex Corporation in Texas, was sold. He had other industry opportunities, but when the University of Kentucky, where he earned his bachelor’s and doctoral degrees, came calling in 1999, Mumper went into academia, taking with him the industry perspective he had gained.
“I think it benefited me in that I was able to see real-world applications of technology in moving those toward commercial products,” he says. “I learned a lot about the FDA and commercializing products. That’s helped me because there is a growing emphasis on translational technology and moving it toward the clinic and having real potential for commercial application. I might not have that same awareness had I not been working in the industry for eight years and thinking about what it takes to translate a technology into a commercial product. So that’s helped me in applying technology to commercial products and writing competitive grants.”
He put that experience to good use at UK. From 1999 to 2007, he was the associate director of the Center for Pharmaceutical Science and Technology, an FDA-registered clinical trial manufacturing facility. The facility, one of only a handful of its kind in the country, works with universities, government, and industry to conduct clinical trial manufacturing. Mumper was the principal investigator on many of the center’s projects, leading the center’s efforts to complete seven full product developments that resulted in human clinical trials.
Along the way, he built a diverse funding portfolio that included twenty-four grants and contracts from federal or foundation sources and thirty-nine from industry.
“Getting funded in an academic environment has changed dramatically in the last five years; it’s getting much more difficult,” he says. “I’ve been fortunate to have a portfolio of funding from both industry and federal sources, and I attribute that to the fact that I understand and appreciate the needs of industrial companies. So I’m able to put together proposals and do work that’s very related to meeting their needs.”
From Nanoparticles to Blackberries
Mumper’s research interest lies in finding better ways to deliver potent drugs by various routes of administration, and nanotechnology is the crux of his work. He has worked on using nanoparticles to deliver drugs and vaccines, as well as developing topical formulations and microbicides. He also cofounded a company, NanoMed Pharmaceuticals Inc, which is currently developing nanoparticle-based delivery systems for anticancer drugs.
One of the projects he worked on while at the University of Kentucky’s Center for Pharmaceutical Science and Technology took him in what appeared to be a completely different direction. Researchers at Ohio State University had been conducting research to see if freeze-dried black raspberries could be developed into a topical gel that would prevent pre-cancerous lesions from becoming oral cancer, since the anthocyanin in the berries have strong antioxidant and anti-inflammatory properties. They contracted the CPST to develop a formulation and to conduct a Phase I clinical study.
The clinical trial produced promising results as well more than half of the patients in the study showed stabilization of disease and/or improvement. Media reports about the study caught the attention of Paige Shumate Short, owner of Windstone Farms, the largest blackberry grower in Kentucky. She approached Mumper about starting a company, Four Tigers LLC, to develop potential health and medical products based on the extracts of blackberries, which are related to black raspberries.
With the capacity to grow one hundred and fifty acres of blackberries, Windstone Farms was looking to expand its business opportunities to beyond jams and preserves. Therefore, Four Tigers is developing products—such as blackberry extract chewing gum and blackberry extract lotion—that would have near-term product opportunities while also having the potential for medicinal use. Because these near-term products are not classified as drugs, such products are not as heavily regulated by the FDA and can reach market much more quickly.
“But at the same time, every one of those products can be pursued as an FDA-registered ‘botanical drug product’ if you can find and prove that it is efficacious and safe in treating a disease, and that’s along the lines of where my interests are,” Mumper says.
“For instance, on one hand, the blackberry extract gum could be a food that could be marketed very quickly on the shelf. But we are in the process of facilitating a Phase I clinical study to see if that blackberry extract gum can prevent gingivitis and periodontal disease because of its potent anti-inflammatory properties. The blackberry extract lotion could be marketed as a cosmetic to beautify the skin, but we are also investigating whether or not a blackberry lotion would prevent UV-induced damage to skin and therefore prevent skin cancer. The blackberry extract capsule could be a dietary supplement—no medical claims, just general health benefits—but we are also investigating through a UNC collaborator whether or not the extract would be helpful in preventing various GI-inflammatory diseases, such as Crohn’s disease, ulcerative colitis, and irritable bowel syndrome.”
Working with collaborators at OSU, Mumper has developed a mucoadhesive blackraspberry gel to prevent oral cancer. The gel will be entering a multi-center phase II clinical study in 2009-10.
Blackberries and nanoparticles might seem worlds apart, but Mumper sees a similarity between them: They are both tools for drug discovery and drug development.
“You might say, ‘Fruits and nanotechnology?’ But there is a loose common theme, and that is using drug formulations to increase the potency of compounds or drugs,” he says. “These compounds could be anticancer drugs. They could be subunit protein vaccines, like HIV proteins. They could be components of these fruit extracts, like these anthocyanins that have incredible oxidant, anti-inflammatory, and anti-proliferative properties. But they are not stable, and you need to find better ways to formulate and deliver them.”